Zinc is an essential cofactor for many enzymes active in metabolism and signal transduction and in proteins, such as transcription factors that control gene expression. For humans, it is estimated that about 3000 proteins (10% of all proteins) contain zinc as a cofactor. Zinc has critical roles in every cell both as a structural element and a dynamic signaling ion, released within the cell or to the extracellular milieu. This ion has important functions in the nervous, reproductive and immune systems, and a central role in development and growth. An exciting progress in recent years is the recognition that Zn2+ ions have functions as messengers in cellular information transfer. Both intercellular and intracellular signaling functions of Zn2+ affect pathways that control proliferation, differentiation and apoptosis.
Given the fundamental functions of zinc in cell biology, it comes as no surprise that perturbations of the homeostatic mechanisms that regulate cellular Zn2+ are involved in many diseases, including degenerative diseases, such neurodegeneration (Alzheimer disease, stroke), diabetes, cancer, and wound healing. The World Health Organization considers zinc deficiency as the 5th leading cause of morbidity and mortality in developing countries (11th worldwide). The clinical symptoms of severe zinc deficiency in humans include dermatitis, diarrhea, alopecia, re-current infections (pneumonia) and neurological disturbances. In children, it is also a cause for stunted growth, including stunted sexual maturation in boys.
An important recent development is the recognition that mutations in proteins that control cellular zinc homeostasis are the cause for various diseases. Intriguing association have been discovered between zinc transporters and diseases. Among them: Type1 and type2 diabetes are genetically associated with mutations in ZnT8, Acrodermatitis entheropathica, a genetic disorder due to mutations in the transporter Zip4 and fatal if not treated with zinc, and diseases that affect a variety of organs (heart, intestine, liver).
The last few years have witnessed dramatic progress on all frontiers of Zn2+ biology aided by powerful new tools, such as highly-specific fluorescent zinc probes, and transgenic animal models. The sensitivity and specificity of these techniques has resulted in increased understanding of many novel aspects of the physiological and pathophysiological functions of zinc. Progress has been especially pronounced with regard to the activity and functions of zinc in the central nervous system, where synaptically released Zn2+ interacts with the receptors of major neurotransmitters (GABA, NMDA and glycine) and influences important physiological and patho-physiological processes, including long-term potentiation (LTP), memory consolidation and neurodegeneration.
The Network for the Biology of Zinc